Central Insulin Modulates Dopamine Signaling in the Human Striatum

Author:

Kullmann Stephanie123ORCID,Blum Dominik4,Jaghutriz Benjamin Assad123,Gassenmaier Christoph5,Bender Benjamin6,Häring Hans-Ulrich123,Reischl Gerald7,Preissl Hubert12389ORCID,la Fougère Christian410,Fritsche Andreas123,Reimold Matthias410,Heni Martin12311ORCID

Affiliation:

1. Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Germany

2. German Center for Diabetes Research (DZD), Tübingen, Germany

3. Department of Internal Medicine, Division of Endocrinology, Diabetology and Nephrology, Eberhard Karls University Tübingen, Tübingen, Germany

4. Department of Nuclear Medicine and Clinical Molecular Imaging, Eberhard-Karls-University Tübingen, Tübingen, Germany

5. Department of Internal Medicine, Division of Hematology, Oncology, Clinical Immunology and Rheumatology, Eberhard Karls University Tübingen, Tübingen, Germany

6. Department of Diagnostic and Interventional Neuroradiology, University Hospital Tübingen, Tübingen, Germany

7. Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany

8. Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany

9. Department of Pharmacy and Biochemistry, Institute of Pharmaceutical Sciences, Eberhard Karls University Tübingen, Tübingen, Germany

10. Cluster of Excellence iFIT (EXC 2180) “Image Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, Germany

11. Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital Tübingen, Tübingen, Germany

Abstract

Abstract Objective Activity in the dopaminergic pathways of the brain is highly sensitive to body weight and metabolic states. Animal studies show that dopamine neurons are important targets for the metabolic hormone insulin with abolished effects in the insulin-resistant state, leading to increases in body weight and food intake. In humans, the influence of central acting insulin on dopamine and effects of their interplay are still elusive. Research Design and Methods We investigated whether central administered insulin influences dopaminergic activity in striatal regions and whole-brain neural activity. Using a positron emission tomography (PET)/magnetic resonance imaging (MRI) hybrid scanner, we simultaneously performed [11C]-raclopride-PET and resting-state functional MRI in 10 healthy normal-weight men after application of intranasal insulin or placebo on 2 separate days in a randomized, placebo-controlled, blinded, crossover trial. Results In response to central insulin compared with placebo administration, we observed greater [11C]-raclopride binding potential in the bilateral ventral and dorsal striatum. This suggests an insulin-induced reduction in synaptic dopamine levels. Resting-state striatal activity was lower 15 and 30 minutes after nasal insulin compared with placebo. Functional connectivity of the mesocorticolimbic circuitry associated with differences in dopamine levels: individuals with a stronger insulin-induced effect on dopamine levels showed a stronger increase in functional connectivity 45 minutes after intranasal insulin. Conclusions This study indicates that central insulin modulates dopaminergic tone in the striatum, which may affect regional brain activity and connectivity. Our results deepen the understanding of the insulin-dopamine interaction and the complex network that underlies the regulation of whole-body metabolism.

Funder

Federal Ministry of Education and Research

German Center for Diabetes Research

Publisher

The Endocrine Society

Subject

Biochemistry, medical,Clinical Biochemistry,Endocrinology,Biochemistry,Endocrinology, Diabetes and Metabolism

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